New review examines oral cancer drug delivery barriers and strategies

Delivering drugs directly to oral tumor sites remains challenging. A recent review involving researchers from Hasanuddin University examines barriers to local drug delivery and analyses strategies for targeting oral cancer lesions. Saliva, chewing, tongue movement, and individual tumor characteristics can affect how long a medicine remains at the treatment site and how consistently it is released. Researchers emphasize tailoring delivery systems to the tumor, drug, and patient alongside realistic testing under clinical conditions.

A new review by a team of researchers from Indonesia, Japan, and China, led by Professor Nurhasni Hasan from the Faculty of Pharmacy, Hasanuddin University, Indonesia, examines how emerging local drug delivery systems could be designed to overcome the barriers in treating oral squamous cell carcinoma (OSCC). It is one of the most common malignancies affecting the oral cavity and head and neck region, and one that contributes significantly to the global burden of cancer-related morbidity and mortality.

Treating oral cancer with drugs delivered directly to the lesion site is a promising approach. This requires that the medicine must remain at the cancer site long enough to provide sustained treatment, facilitating increased drug exposure to the tumor while reducing unwanted exposure throughout the body. But there is a fundamental challenge: the mouth is constantly working against the medicine, creating what the authors describe as stringent “hard constraints” for effective local drug delivery. Saliva can dilute and wash away medicines, while enzymes, chewing, speaking, and tongue movement can degrade or dislodge drug-delivery systems used for the treatment.

The review was made available online on May 21, 2026, and published in Volume 225 of the European Journal of Pharmaceutics and Biopharmaceutics on August 1, 2026, brings together different approaches to local OSCC treatment, including mucoadhesive films and patches, oral sprays, in-situ gels and injectable hydrogels. Rather than treating these technologies as one-size-fits-all solutions, the researchers emphasize that the best delivery system may depend on the characteristics of both the drug and the tumor.

“There is a tendency to think of drug delivery as a problem that can be solved by developing a better formulation,” explains Prof. Hasan, “However, the bigger question is whether the formulation is appropriate for that particular clinical situation.”

Depending on the shape and location, a flat, accessible lesion would be suitable for mucoadhesive films that remains attached to the mucosa while delivering the drug. However, lesions which are irregular or infiltrative may benefit from gels or injectable hydrogels that can conform to complex tissue surfaces and provide more sustained drug exposure, delivering the drug to deeper layers. Sprays are comparatively convenient in application but have shorter residence rate due to salivary clearance.

Moreover, the oral environment also undergoes changes during cancer treatment. Radio therapy and chemotherapy often result in xerostomia, or dry mouth, and mucosal damage, affecting hydration, lubrication, drug release, and adhesion. Increase in salivary flow leads to acceleration in dilution and clearance. Thus, indicating that formulations tested under simplified laboratory conditions may not perform in the same way in patients.

The researchers state that a more realistic evaluation of local drug-delivery systems is required. They emphasize that the future studies should focus on how well formulations remain attached under salivary flow and mechanical stress, maintain stability against changes in pH and enzymatic activity, and deliver drugs consistently to tumor margins. Additionally, the review also assessed the translational maturity of different types of formulations.

“A sophisticated technology has limited clinical value if it is difficult to manufacture, administer, or tolerate. These practical considerations must guide formulation development from the start,” notes Prof. Hasan.

Mucoadhesive films and patches currently appear to have stronger near-term potential because similar buccal delivery formats already have regulatory and manufacturing precedent. Injectable hydrogels, on the other hand, offer promising options for irregular lesions but face additional challenges involving manufacturing, gelation, degradation, clinical application, and long-term biocompatibility.

Notably, these technologies are not yet established treatments for OSCC. Thus, the review provides a framework for moving promising approaches toward clinical use by matching the delivery system to the drug, tumor, and conditions experienced by individual patient.

Taken together, the researchers suggest that the next generation of local oral cancer therapies should be designed to keep the right amount of drug at the right place for the right length of time and not merely for drug delivery. “The goal should be to make local treatment more predictable. We need delivery systems that researchers can evaluate consistently and clinicians can realistically use,” concludes Prof. Hasan.